2023 Fiscal Year Final Research Report

Understanding the molecular mechanisms underlying chemical-induced intracellular receptor signaling disruption and sensitivity in aquatic mammals

Research Project

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Project/Area Number	19H01150
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 63:Environmental analyses and evaluation and related fields
Research Institution	Ehime University
Principal Investigator	IWATA Hisato 愛媛大学, 沿岸環境科学研究センター, 教授 (10271652)
Co-Investigator(Kenkyū-buntansha)	国末達也愛媛大学, 沿岸環境科学研究センター, 教授 (90380287) 石橋弘志愛媛大学, 農学研究科, 准教授 (90403857)
Project Period (FY)	2019-04-01 – 2024-03-31
Keywords	水棲哺乳類 / 細胞内受容体 / 感受性 / in vitro / in silico / 環境汚染物質
Outline of Final Research Achievements	1. We developed a semi-quantitative analytical method for unknown substances in 11 cetacean species that were difficult to detect using conventional methods. In addition to legacy persistent organic pollutants (POPs), we identified a large number of marine natural products and unknown substances. 2. We established a new in vitro cytotoxicity assay using stranded porpoise fibroblast cells and evaluated the cytotoxicity of environmental contaminants. We succeeded in directly differentiating the somatic cells of melon-headed whales into neuronal cells and revealed the neurotoxicity of 4'OH-CB72. 3. We evaluated the activation potencies of Baikal seal constitutive androgen receptor (CAR) and estrogen receptors α and β (bsER) by environmental contaminants. We also constructed a machine learning model to predict the agonist activity of environmental contaminants mediated by bsERs.
Free Research Field	環境毒性学
Academic Significance and Societal Importance of the Research Achievements	OECDは、化学物質安全性評価の新たな手法として、「試験・評価の統合的アプローチ（IATA）」を提唱している。OECDは、IATAを発展させることによって、従来のin vivo試験に代えて、in vitro・in silico研究で生み出された技術を化学物質安全性評価に適用しようと模索している。ところが、これら先端技術（NAMs）が環境生物へ適用された例は、我々の研究グループの成果以外、僅少である。したがって、水棲哺乳類の受容体や細胞を対象に、有害性・リスクを評価した本研究は学術的に新規性の高い試みである。